Once inside the mitochondrion, the dominant way that the bound fatty acids are used as fuel in cells is through β-oxidation, which cleaves two carbons off of the acyl-CoA molecule in every cycle to form acetyl-CoA.[24] Acetyl-CoA enters the citric acid cycle, where it undergoes an aldol condensation with oxaloacetate to form citric acid; citric acid then enters the tricarboxylic acid cycle (TCA), which harvests a very high energy yield per carbon in the original fatty acid.[25][26]
The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control (refractory) epilepsy in children. The diet forces the body to burn fats rather than carbohydrates. Normally, the carbohydrates contained in food are converted into glucose, which is then transported around the body and is particularly important in fueling brain function. However, if little carbohydrate remains in the diet, the liver converts fat into fatty acids and ketone bodies. The ketone bodies pass into the brain and replace glucose as an energy source. An elevated level of ketone bodies in the blood, a state known as ketosis, leads to a reduction in the frequency of epileptic seizures.[1] Around half of children and young people with epilepsy who have tried some form of this diet saw the number of seizures drop by at least half, and the effect persists even after discontinuing the diet.[2] Some evidence indicates that adults with epilepsy may benefit from the diet, and that a less strict regimen, such as a modified Atkins diet, is similarly effective.[1] Potential side effects may include constipation, high cholesterol, growth slowing, acidosis, and kidney stones.[3]
^ Lockyer, Christina (1991). "Body composition of the sperm whale, Physeter cation, with special reference to the possible functions of fat depots" (PDF). Journal of the Marine Research Institute. 12 (2). ISSN 0484-9019. Retrieved 2014-04-25. The significant levels of carbohydrate, probably mostly in the form of glycogen, in both blubber and muscle, may represent an instant form of energy for diving via anaerobic glycolysis.
If you’re serious about maximizing the benefits of ketosis, then forego coconut oil, MCT liquid oil, olive oil, etc. and instead use Brain Octane as your oil of choice for recipes like bulletproof coffee, or in teas, salad dressings, or as a sushi or entrée flavor enhancer. For a slightly less expensive, but not quite as effective form of MCT, use XCT oil.
There are so many tricks, shortcuts, and gimmicks out there on achieving optimal ketosis – I’d suggest you don’t bother with any of that. Optimal ketosis can be accomplished through dietary nutrition alone (aka just eating food). You shouldn’t need a magic pill to do it. Just stay strict, remain vigilant, and be focused on recording what you eat (to make sure your carb and protein intake are correct).
I asked James Fell if he had some practical advice on sustainable dieting. “When it comes to weight loss,” he said, “the only thing that matters is caloric deficit. However, quality of diet affects quantity. A higher quality diet is more likely to be one that allows you to eat a lower quantity of calories and still be satisfied. That being said, there are many different ways to find a high-quality diet.”
Ben. I do not read epidemiological studies anymore… Just biology. There are plenty of examples of traditional cultures consuming high carb (and high fat) without any of the health issues those studies in your article claim. So either high fat or high carb both work if done properly… AND in the right environment. Both are ancestral not just one of the two and have posit and negat because it has to do with the climate and environment around. I do not listen to anybody that pushes JUST one because they are ignoring the reality. I hope you join this "common sense" wagon.
-Nervous System Damage: It’s been shown that patients with neuropathy whose after-meal glucose readings were above the diabetic threshold sustained damage to their large nerve fibers. Even neuropathy patients whose glucose readings remained well within the normal range showed damage to their small nerve fibers. Studies have shown that within any blood sugar range, the higher the glucose, the greater the damage to nerve fibers.

These affect your brain and spine, as well as the nerves that link them together. Epilepsy is one, but others may be helped by a ketogenic diet as well, including Alzheimer’s disease, Parkinson’s disease, and sleep disorders. Scientists aren’t sure why, but it may be that the ketones your body makes when it breaks down fat for energy help protect your brain cells from damage.

Other research further supports the potential benefits of this diet. For example, preliminary studies link following the keto diet to reduced symptoms of Alzheimer’s disease. (4) Previous research suggests it may also help reverse metabolic syndrome, manage Parkinson’s disease, has been proven to help control seizures in children with epilepsy, and, according to the results of a small pilot study, may potentially even improve symptoms of polycystic ovary syndrome (PCOS). (5, 6, 7)


Under these circumstances, as soon as the body’s limited reserves of glucose starts to run out, your entire body switches its fuel supply to run almost completely on fat. The levels of the fat-storing hormone insulin levels become very low, and fat burning increases dramatically. You thus get easy access your fat stores, and can burn them off. This is great for losing excess weight. Studies prove that keto diets result in more weight loss, faster. There are also more potential benefits.

The brain is composed of a network of neurons that transmit signals by propagating nerve impulses. The propagation of this impulse from one neuron to another is typically controlled by neurotransmitters, though there are also electrical pathways between some neurons. Neurotransmitters can inhibit impulse firing (primarily done by γ-aminobutyric acid, or GABA) or they can excite the neuron into firing (primarily done by glutamate). A neuron that releases inhibitory neurotransmitters from its terminals is called an inhibitory neuron, while one that releases excitatory neurotransmitters is an excitatory neuron. When the normal balance between inhibition and excitation is significantly disrupted in all or part of the brain, a seizure can occur. The GABA system is an important target for anticonvulsant drugs, since seizures may be discouraged by increasing GABA synthesis, decreasing its breakdown, or enhancing its effect on neurons.[7]

Con: Results can vary depending on how much fluid you drink. By drinking more water, you dilute the concentration of ketones in the urine and thus a lower level of ketones will be detected on the strips. The strips don’t show a precise ketone level. Finally, and most importantly, as you become increasingly keto-adapted and your body reabsorbs ketones from the urine, urine strips may become unreliable, even if you’re in ketosis.
Con: Results can vary depending on how much fluid you drink. By drinking more water, you dilute the concentration of ketones in the urine and thus a lower level of ketones will be detected on the strips. The strips don’t show a precise ketone level. Finally, and most importantly, as you become increasingly keto-adapted and your body reabsorbs ketones from the urine, urine strips may become unreliable, even if you’re in ketosis.
The ketogenic diet is a medical nutrition therapy that involves participants from various disciplines. Team members include a registered paediatric dietitian who coordinates the diet programme; a paediatric neurologist who is experienced in offering the ketogenic diet; and a registered nurse who is familiar with childhood epilepsy. Additional help may come from a medical social worker who works with the family and a pharmacist who can advise on the carbohydrate content of medicines. Lastly, the parents and other caregivers must be educated in many aspects of the diet for it to be safely implemented.[5]
Since originally publishing this article, I’ve been asked whether elevating blood ketones with exogenous sources could trigger a ketone-induced release of insulin that would theoretically reduce hepatic ketogenesis and perhaps slow fat mobilization. This makes sense since you are putting more energy into the system in general (from exogenous ketones), so there would be less need to draw off your own fat stores.
Thanks for all of the great info!! I have Hashimoto’s and would really like to try a high fat/low carb diet. You mentioned that this might not be a good option for people with thyroid issues. How do you recommend I modify my diet to lose weight taking into consideration the Hashimoto’s. I take Westhroid, a non-synthetic thyroid supplement to help with my sluggish thyroid. Thanks so much for any advice you can give me. :)
Take coconut oil for example. The coconut oil industry loves to market the idea that relatively inexpensive and abundant coconut oil is a great source of MCTs because it’s “62% MCT oil”, but the problem is that studies show you can’t get many useful ketogenic MCT’s from just eating coconut oil or even most brands of “MCT oil”, which are often is diluted with lauric acid, a cheap, hugely abundant part of coconut oil that is typically marketed as an MCT oil.

As insulin levels plummet from carb-cutting, more water is flushed out, along with excess sodium (in contrast, excess insulin from carbs causes sodium and water retention).4 In some people, dehydration contributes to constipation, which can also result from avoiding fiber-rich carbohydrate foods. While less common, diarrhea or loose bowels can be triggered by a number of factors including too much or too little fat, dairy intolerance, or changes in gut flora. 

Wow! Amazing article. I don’t read blogs regularly, but I’ll be reading more of yours. I am on day 11 of a fast to get me into ketosis; 7 days bone broth and now on day-4 water only. Intentions are weight loss (10# down, 15# more to go) and immunity improvement/gut help. Planning 9 days of whey water, fermented veggies and mad probiotics when the water days are done (day 14?). After this fast I want to stay fat adapted, start training again and get down to 8% body fat. I believe you have cut that journey significantly with this article. Thank you.
“Muscle loss on the ketogenic diet is an ongoing area of research,” says Edwina Clark, RD, a dietitian in private practice in San Francisco. “Small studies suggest that people on the ketogenic diet lose muscle even when they continue resistance training. This may be related to the fact that protein alone is less effective for muscle building than protein and carbohydrates together after exercise.” Meanwhile, according to a small study published in March 2018 in the journal Sports, people following the keto diet for three months lost about the same amount of body fat and had about the same muscle mass changes as people following normal diets. Yet the folks on keto did lose more leg muscle.
-Cancer: Numerous studies have found that the risk for cancer increases with high blood sugar, which makes sense, since cancer cells feed primarily on glucose. This includes cancers of the endometrium, pancreas, and colon and colorectal tumors. Tim Ferriss recently hosted a fantastic article by Peter Attia about this very issue, and how ketosis may indeed be a potential cancer cure.
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Although many hypotheses have been put forward to explain how the ketogenic diet works, it remains a mystery. Disproven hypotheses include systemic acidosis (high levels of acid in the blood), electrolyte changes and hypoglycaemia (low blood glucose).[19] Although many biochemical changes are known to occur in the brain of a patient on the ketogenic diet, it is not known which of these has an anticonvulsant effect. The lack of understanding in this area is similar to the situation with many anticonvulsant drugs.[56]
Ketone bodies are acidic, but acid-base homeostasis in the blood is normally maintained through bicarbonate buffering, respiratory compensation to vary the amount of CO2 in the bloodstream, hydrogen ion absorption by tissue proteins and bone, and renal compensation through increased excretion of dihydrogen phosphate and ammonium ions.[9] Prolonged excess of ketone bodies can overwhelm normal compensatory mechanisms, defined as acidosis if blood pH falls below 7.35.
And it all culminated with me stepping into Dr. Jeff Volek’s world famous laboratory at University of Connecitut to subject myself to extensive blood testing, chunks of muscle removed from my legs, fat sucked out of my butt-cheeks, urine, stool and gut microbiome testing, oxygen and carbon dioxide testing and countless hours of treadmill running to discover what a full twelve months of eating a ketotic diet had actually done to my body.
It also means that if you’re a very active athlete or exercise enthusiast and you’re following “trickle-down” advice from the sedentary or less active ketosis experts to eat less than 40g of carbs per day, you’re making a big mistake when it comes to your hormonal balance, and you need to up your carbohydrate intake to 100-200g of carbs per day. You’d be surprised at how easy it is (if you’re a very active person) to stay in ketosis on this level of carbohydrate intake. Go ahead. Do Ketonix breath testing to prove me wrong. You can eat boatloads of carbohydrates at night and be back in ketosis within just two to three hours. When you combine that with the cutting-edge tricks you’re about to learn, you’ll find that you can toss hormonal issues out the window, get into ketosis, have your cake, and eat it too. Literally.
^ Hochachka PW, Storey KB (February 1975). "Metabolic consequences of diving in animals and man". Science. 187 (4177): 613–21. Bibcode:1975Sci...187..613H. doi:10.1126/science.163485. PMID 163485. In the terminal stages of prolonged diving, however, even these organs must tolerate anoxia for surprisingly long times, and they typically store unusually large amounts of glycogen for this purpose.
^ Jump up to: a b Sinclair, H. M. (1953). "The Diet of Canadian Indians and Eskimos" (PDF). Proceedings of the Nutrition Society. 12 (1): 69–82. doi:10.1079/PNS19530016. ISSN 0029-6651. It is, however, worth noting that according to the customary convention (Woodyatt, 1921 ; Shaffer, 1921) this diet is not ketogenic since the ratio of ketogenic(FA) to ketolytic (G) aliments is 1.09. Indeed, the content of fat would have to exactly double (324 g daily) to make the diet ketogenic (FA/G>1–5).
I have that thing on a “real” ketogenic diet where I wake up at 3 am with my mind/heart racing and can’t sleep. It happens the very first day I reduce my carbs and continues as long as my carbs are reduced (5 weeks is the longest I’ve been able to put up with this to see if I could fix it and stay ketogenic). Magnesium and/ or cal-mag before bed does not help. Is carb loading at night the only hope for fixing this? I already take great care with bluelight and EMF.

Long-term use of the ketogenic diet in children increases the risk of slowed or stunted growth, bone fractures, and kidney stones.[18] The diet reduces levels of insulin-like growth factor 1, which is important for childhood growth. Like many anticonvulsant drugs, the ketogenic diet has an adverse effect on bone health. Many factors may be involved such as acidosis and suppressed growth hormone.[38] About one in 20 children on the ketogenic diet develop kidney stones (compared with one in several thousand for the general population). A class of anticonvulsants known as carbonic anhydrase inhibitors (topiramate, zonisamide) are known to increase the risk of kidney stones, but the combination of these anticonvulsants and the ketogenic diet does not appear to elevate the risk above that of the diet alone.[39] The stones are treatable and do not justify discontinuation of the diet.[39] Johns Hopkins Hospital now gives oral potassium citrate supplements to all ketogenic diet patients, resulting in one-seventh of the incidence of kidney stones.[40] However, this empiric usage has not been tested in a prospective controlled trial.[9] Kidney stone formation (nephrolithiasis) is associated with the diet for four reasons:[39]
You indicate that exogenous ketones do not shut down the ability, of your body, to oxidize fat. Is that to say it does not have an effect on your body at all? My specific question is… does my body oxidize less fat, when supplementing with exogenous ketones? I think you indicate in your article that it could. I would expect it to, in that if I supplement then my body would not “need” to oxidize the fat to provide the energy.
Here’s what we do know: The keto diet may be useful in treating symptoms of epilepsy, a seizure disorder. “The use of keto in treating epilepsy has the most evidence,” Angelone says. One study conducted by Johns Hopkins Medicine, for example, followed epileptic patients on the keto diet and found that 36 percent of them had a 50 percent reduction in seizures after three months on the diet, and 16 percent were seizure-free. However, experts aren't entirely sure why the keto diet has this affect, she adds.
Since originally publishing this article, I’ve been asked whether elevating blood ketones with exogenous sources could trigger a ketone-induced release of insulin that would theoretically reduce hepatic ketogenesis and perhaps slow fat mobilization. This makes sense since you are putting more energy into the system in general (from exogenous ketones), so there would be less need to draw off your own fat stores.
Around this time, Bernarr Macfadden, an American exponent of physical culture, popularised the use of fasting to restore health. His disciple, the osteopathic physician Dr. Hugh William Conklin of Battle Creek, Michigan, began to treat his epilepsy patients by recommending fasting. Conklin conjectured that epileptic seizures were caused when a toxin, secreted from the Peyer's patches in the intestines, was discharged into the bloodstream. He recommended a fast lasting 18 to 25 days to allow this toxin to dissipate. Conklin probably treated hundreds of epilepsy patients with his "water diet" and boasted of a 90% cure rate in children, falling to 50% in adults. Later analysis of Conklin's case records showed 20% of his patients achieved freedom from seizures and 50% had some improvement.[10]
Selecting the right food will be easier as you become accustomed to the Keto approach. Instead of lean meats, you’ll focus on skin-on poultry, fattier parts like chicken thighs, rib-eye steaks, grass-fed ground beef, fattier fish like salmon, beef brisket or pork shoulder, and bacon. Leafy greens such as spinach, kale and lettuce, along with broccoli, cauliflower and cucumbers, make healthy vegetable choices (but you’ll avoid starchy root foods like carrots, potatoes, turnips and parsnips). You can work in less-familiar veggies such as kohlrabi or daikon.
This answer made me sad. Having lived in New York all of my life, I from a young age saw loved ones fall victim to spontaneous gluten intolerance and restaurants run to their rescue with accommodating menus.  This is why I get annoyed. What’s a dietary prescription for someone who wants to go to a dinner party and be able to eat a meal that was prepared for them? Keto is cultish not for its members’ radical commitment to a dietary restriction but for their lack of full participation in the outside world.
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